Dr Hamilton on Maintenance Tucatinib-Based Therapy for HER2+ Breast Cancer

“There’s now an option for all patients for maintenance, regardless of hormone receptor status.”

Erika P. Hamilton, MD, director of Breast Cancer and Gynecologic Cancer Research at Sarah Cannon Research Institute, discussed how the FDA approval of tucatinib (Tukysa) plus trastuzumab (Herceptin) and pertuzumab (Perjeta) as first-line maintenance therapy fits into the evolving treatment landscape for advanced HER2-positive breast cancer.

On October 7, 2026, the FDA approved tucatinib in combination with trastuzumab and pertuzumab for the maintenance treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer following induction therapy. The decision was supported by data from the phase 3 HER2CLIMB-05 trial (NCT05132582), in which the tucatinib triplet reduced the risk of disease progression or death by 35.9% vs placebo plus trastuzumab and pertuzumab (HR, 0.64; 95% CI, 0.51-0.80; 2-sided P < .0001).

The approval adds another option for patients in the first-line maintenance setting, Hamilton said. The palbociclib (Ibrance)–containing phase 3 PATINA trial (NCT02947685) regimen is approved for first-line maintenance only in the subset of patients whose tumors are estrogen receptor (ER)–positive, whereas HER2CLIMB-05 enrolled all patients regardless of ER status, she noted.

Both the HER2CLIMB-05 and PATINA maintenance strategies were designed around induction with trastuzumab, pertuzumab, and a taxane (THP) and predate results from the phase 3 DESTINY-Breast09 study (NCT04784715), which led to the FDA approval of first-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab for patients with HER2-positive disease. She expects the palbociclib-based PATINA regimen to be used heavily in ER-positive disease, whereas the HER2CLIMB-05 regimen, although also an option in ER-positive disease, will be used heavily in ER-negative disease.

The nuance, Hamilton said, is that DESTINY-Breast09 evaluated T-DXd plus pertuzumab and did not allow for a maintenance regimen. Even so, she noted that breast oncology moves at a fast pace, and sometimes treatment approaches must evolve and be integrated into practice without the availability of robust randomized data. She also anticipated a strong desire for a maintenance strategy among patients.

Rather than treating for a set 6 cycles and stopping, as is done with THP, Hamilton said she will want to treat until maximal response when using a T-DXd–based approach, which data suggest can take longer than 1 year to reach. Once patients reach maximal response, she will consider stopping and transitioning to a maintenance regimen, and that is where the HER2CLIMB-05 regimen will come in for her.